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Yet how interictal hypercapnic cardioventilatory responses vary by seizure phenotype is unclear. We aimed to determine whether central chemoreception and autonomic regulation differ across epilepsy phenotypes during a standardized CO\n                      <jats:sub>2<\/jats:sub>\n                      challenge. We hypothesized that rats with chronic generalized tonic\u2013clonic seizures would show impaired hypercapnic cardioventilatory and autonomic responses compared with rats with generalized absence seizures and healthy controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We measured breathing\u00a0frequency (f\n                      <jats:sub>B<\/jats:sub>\n                      ), heart rate (HR), and heart rate variability (HRV) before, during, and after a 1\u2009h 10% CO\n                      <jats:sub>2<\/jats:sub>\n                      exposure in three groups of male rats: kainic acid (KA; tonic\u2013clonic), genetic absence epilepsy rat from Strasbourg (GAERS; absence), and Wistar controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Controls showed increased f\n                      <jats:sub>B<\/jats:sub>\n                      and decreased HR during hypercapnia. KA rats exhibited blunted f\n                      <jats:sub>B<\/jats:sub>\n                      and HR responses; GAERS displayed preserved f\n                      <jats:sub>B<\/jats:sub>\n                      elevation with faster post\u2010challenge normalization and intermediate HR changes. Coupling of f\n                      <jats:sub>B<\/jats:sub>\n                      and HR collapsed during CO\n                      <jats:sub>2<\/jats:sub>\n                      in both epilepsy groups and re\u2010emerged in recovery. In KA rats, Stage 3\u20134 seizure burden positively correlated with HR during hypercapnia. HRV reactivity to hypercapnia was robust in controls, attenuated in GAERS, and largely absent in KA, whereas interictal baseline HRV did not differ among the groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      These data support seizure\u2010type\u2013specific disruption of chemoreflex\u2013autonomic integration. Extending clinical hypercapnic ventilatory response (HCVR) testing, a hypercapnic cardioventilatory response (HCCVR), that is, a combined f\n                      <jats:sub>B<\/jats:sub>\n                      , HR, and HRV readout, may help to refine SUDEP risk stratification beyond seizure frequency and type.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70123","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:50:10Z","timestamp":1771339810000},"page":"2613-2627","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Seizure\u2010type\u2013specific disruption of hypercapnic cardioventilatory responses in epilepsy models"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-197X","authenticated-orcid":false,"given":"Ayse S.","family":"Dereli","sequence":"first","affiliation":[{"name":"Clinical Neuroscience, 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